DURING a lecture last year, British Indian chemist Professor Sir Shankar Balasubramani an urged policymakers to continue funding academic research to push the boundaries of science. “Unless we strongly fund basic science, in novation is dead a few years down the line… I don’t think this is fully understood by some of the decision-makers. Everything we have achieved would not have happened if we didn’t get the basic science funding at the beginning,” he said. He spoke about his own experience translat ing his DNA replication research into a cutting edge sequencing technology, which has been used to study the genetic origins of disease and track emerging virus strains during the Covid pandemic. He is currently the Herschel Smith Professor of Medicinal Chemistry at the University of Cambridge and co-invented Solexa sequencing, a technology that was acquired by biotechnology giant Illumina for £600 million in 2007 and that continues to underpin large research initiatives such as the International Cancer Genome Project. “I started my independent academic career in 1994 in the University of Cambridge and have remained there ever since.
I currently hold a joint appointment between the Clinical School and Department of Chemistry. I direct research laboratories in the Department of Chemistry and the CRUK Cambridge Institute at the Addenbrookes Biomedical Campus,” he says about his role. He was awarded the GG2 Outstanding Achievement in Science in 2022 for his contribution to the world of science. Born in Madras (now Chennai), India in 1966, Sir Shankar relocated to the UK with his parents in 1967. He spent his formative years in a rural area near Runcorn, Cheshire, receiving education at Daresbury Primary School and Appleton Hall High School. Married to Veena Krishnan, a general practitioner, they are parents to two children, Sachin and Sashi. He pursued undergraduate studies in Natural Sciences at the University of Cambridge from 1985 to 1988, followed by a PhD supervised by Professor Chris Abell from 1988 to 1991.
Subsequently, he travelled to the US as a SERC/NATO Research Fellow, working under Professor Stephen J Benkovic at Pennsylvania State University from 1991 to 1993. He was persuaded in 1994 to return to Cambridge where he set up his own lab in the department of chemistry. Prof Balasubramanian’s research delves into the chemical biology of nucleic acids, employing principles from chemistry and molecular sciences to tackle significant questions in biology and medicine. His group’s projects are interdisciplinary, allowing for a variety of intellectual and experimental approaches, including organic synthesis, biophysics, molecular and cellular biology, and genomics. A key focus of his research is to understand and manipulate the mechanisms governing gene expression, whether through transcription or translation. He is particularly intrigued by the role of non canonical nucleic acid structures in regulating gene expression. To influence these structures and thereby modulating gene expression, his group tries to design and synthesise small organic molecules. These molecules serve as valuable tools for studying biological mechanisms and offer promising avenues for therapeutics and molecular medicine, especially in diseases characterised by abnormal gene expression such as various cancers. The fundamental research conducted by Prof Balasubramanian’s group also presents opportunities for translation and commercialisation. For instance, Solexa sequencing, a groundbreaking DNA sequencing technology with widespread applications in genomics, including human genome sequencing, emerged from this research. Before assuming his current position, he held roles as a reader and later a professor in Chemical Biology at the University of Cambridge. His contributions to science were recognised with his election as a fellow of the Academy of Medical Sciences in 2011, and he was knighted in the 2017 New Year’s Honours List for his role as a coinventor of New Generation DNA sequencing, hailed as one of the most transformative advances in biology and medicine in decades. In January 2023, he announced that he was excited by potential of Chem-map to understand how drugs interact with the human genome.
He added that Chem-map will make it easier to develop new therapies. It detects the site in the genome where a small molecule binds to genomic DNA or DNA associated proteins. Chem-map allows researchers to conduct in situ mapping of small molecule-genome interactions with unprecedented precision, thanks to an approach known as small-molecule-directed transposase Tn5tagmentation. “Chem-map is a powerful new method to detect the site in the genome where a small molecule binds to DNA or DNA-associated proteins. It provides enormous insights on how some drug therapies interact with the human genome, and makes it easier to develop more effective and safer drug therapies,” Sir Shankar was quoted as saying.
According to reports, Chem-map lifts the lid on the genomic black box by enabling re searchers to detect where small molecule drugs interact with their targets on the DNA genome. Many drugs directly interact with our DNA to treat diseases such as cancer. But even though millions of people are treated with them every year, the molecular mode of action within the genome has remained poorly understood. Prof Balasubramanian is a senior group lead er at the Cancer Research UK Cambridge Insti tute and Fellow of Trinity College, Cambridge. He is recognised for his contributions to the field of nucleic acids. He is a sci entific founder of Solexa and biomodal (formerly Cambridge Epigenetix). In May 2023, the Na tional Academy of Scienc es (NAS) elected Prof Bal asubramanian as the new international mem ber for his distinguished and continuing achievements in original research. Election to NAS is considered one of the highest scientific honours in the US. In 2022, he won the Breakthrough Prize in Life Sciences. Known popularly as the “Oscars of Science,” the Breakthrough Prize recognises the research achievements of the world’s top scientists, awarding approximately $15m (£11.83) annually in prize money. He along with David Klenerman took home the $1.22m (£962,616) Millennium Technology Prize for their work over 27 years creating ever faster and cheaper ways to sequence the hu man genome in 2021. According to a statement, the pair’s Next Generation DNA Sequencing technology (NGS) “means huge benefits to society, from helping the fight against killer diseases such as Covid-19 or cancer, to better understanding crop diseases and enhancing food production.” Twenty years ago, the first attempt to “read” the sequence of 3.2 billion letters that make up the human genome took a decade and cost over a billion dollars. Thanks to Next Generation Sequencing the process can now be performed in one day for just $1,000, and the technology is used over a million times a year, most recently to track cor onavirus mutations during the pandemic. NGS is now widely used in the diagnosis and treatment of some cancers and rare diseases.